Second site reversion of a mutation near the amino terminus of the HIV-1 capsid protein

Claudia S. López, Seyram M. Tsagli, Rachel Sloan, Jacob Eccles, Eric Barklis

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

During HIV-1 morphogenesis, the precursor Gag protein is processed to release capsid (CA) proteins that form the mature virus core. In this process, the CA proteins assemble a lattice in which N-terminal domain (NTD) helices 1-3 are critical for multimer formation. Mature core assembly requires refolding of the N-terminus of CA into a β-hairpin, but the precise contribution of the hairpin core morphogenesis is unclear. We found that mutations at isoleucine 15 (I15), between the β-hairpin and NTD helix 1 are incompatible with proper mature core assembly. However, a compensatory mutation of histidine 12 in the β-hairpin to a tyrosine was selected by long term passage of an I15 mutant virus in T cells. The tyrosine does not interact directly with residue 15, but with NTD helix 3, supporting a model in which β-hairpin folding serves to align helix 3 for mature NTD multimerization.

Original languageEnglish (US)
Pages (from-to)95-103
Number of pages9
JournalVirology
Volume447
Issue number1-2
DOIs
StatePublished - Dec 1 2013

Keywords

  • Capsid
  • Gag
  • HIV
  • N-terminal domain
  • Virus assembly

ASJC Scopus subject areas

  • Virology

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